1. Field of the Invention
This invention pertains to an osmotic device for delivering a useful agent at a controlled and continuous rate over a prolonged period of time to an environment of use.
2. Description of the Prior Art
Devices for the controlled and continuous delivery of an active agent made from microporous materials are known to the prior art. Generally, the agent is embedded in or surrounded by the material and its release therefrom often is adversely influenced by external conditions. For example, U.S. Pat. No. 2,846,057 discloses a device consisting of a porous cellophane wall surrounding sodium fluoride that is released by water flowing into the pores to dissolve and leach it from the device. Controlled release is hard to obtain with this device because release is governed by external conditions and not by the device. That is, the amount of fluoride released changes with the rate of flow of water, with higher rates increasing the amount released, and lower rates decreasing the amount released over time. Similarly, U.S. Pat. No. 3,538,214 discloses a device consisting of drug coated with a film of water-insoluble plastic containing a modifying agent that is soluble at a certain pH. When this device is in the gastrointestinal tract, the modifying agent is partially or fully dissolved from the film by gastrointestinal fluid to form a porous film. This lets fluid through the film to dissolve the drug and leach it outwards through the pores into the tract. Controlled release is difficult to achieve with this device because the selection of the modifying agent is based on the unknown acid and alkaline state of the gastrointestinal tract which concomitantly influences pore formation and the exposure of drug to fluid. A similar device is disclosed in U.S. Pat. No. 2,928,770. The device of this patent consists of an outer layer of drug coated onto a porous material having its pores filled with a softened wax that is supposedly removed in the gastrointestinal tract by the alimentary fluid. This device cannot be relied on for controlled release because it too requires in situ pore formation which is dominated by unregulated external conditions and not by the device.
Another device designed for the release of drug from an inert plastic matrix is described in Acta Pharm. Suecica, Vol. 8, pages 153 to 168, 1971, and in J. Pharm. Sci., Vol. 60 pages 1028 to 1033, 1971. The device disclosed in these references consists of a porous poly(vinylchloride) matrix having drug embedded therein. Several disadvantages are associated with this device that tend to diminish its use as a reliable and dependable device. For example, the rate of release is stirring-rate dependent, as fluid must be in a constant flux to leach drug from the matrix. That is, a slight change in the direction and velocity of fluid can create a turbulence that unpredictably alters the movement of fluid into the pores, and the amount of drug released. Another disadvantage that occurs as drug leaves the device is the length of the diffusional path increases and the surface area of drug decreases. Both events cause the release rate from the matrix to decrease as a function of time. The release rate from the matrix also is pH dependent when a drug is contained therein that has a solubility that is dependent on pH. For these drugs, the amount of drug available for absorption varies with the location of the device in the gastrointestinal tract. A similar device is set forth in U.S. Pat. No. 2,987,445.